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Cyrene: a very reactive bio-based chiral ketone in diastereoselective Passerini reactions

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Abstract

Cyrene, a green bioderived solvent from waste cellulose, was applied to the synthesis of novel α-acyloxyamide derivatives through a Passerini-3CR with carboxylic acids and isocyanides with good yields and diastereoselectivities under mild conditions. Cyrene showed exceptionally high reactivity and the degree of diastereoselection was dependent mostly on the isocyanide. DFT calculations as well as the experimental findings indicated that both kinetic and thermodynamic effects might explain the results.

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References

  1. Hulme C, Dietrich J (2009) Emerging molecular diversity from the intra-molecular Ugi reaction: iterative efficiency in medicinal chemistry. Mol Divers 13:195–207. https://doi.org/10.1007/s11030-009-9111-6

    Article  PubMed  CAS  Google Scholar 

  2. Banfi L, Basso A, Lambruschini C, Moni L, Riva R (2021) The 100 facets of the Passerini reaction. Chem Sci 12:15445–15472. https://doi.org/10.1039/d1sc03810a

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Lambruschini C, Moni L, Banfi L (2020) Diastereoselectivity in Passerini reactions of chiral aldehydes and in Ugi reactions of chiral cyclic imines. Eur J Org Chem 2020:3766–3778. https://doi.org/10.1002/ejoc.202000016

    Article  CAS  Google Scholar 

  4. Vlahoviček-Kahlina K, Vazdar M, Jakas A et al (2018) Synthesis of glycomimetics by diastereoselective Passerini reaction. J Org Chem 83:13146–13156. https://doi.org/10.1021/acs.joc.8b01874

    Article  PubMed  CAS  Google Scholar 

  5. Forconesi GV, Banfi L, Basso A et al (2020) Synthesis of polyoxygenated heterocycles by diastereoselective functionalization of a bio-based chiral aldehyde exploiting the Passerini reaction. Molecules 25:3227. https://doi.org/10.3390/molecules25143227

    Article  CAS  Google Scholar 

  6. Moni L, Banfi L, Basso A et al (2016) Diastereoselective Passerini reaction of biobased chiral aldehydes: divergent synthesis of various polyfunctionalized heterocycles. Org Lett 18:1638–1641. https://doi.org/10.1021/acs.orglett.6b00487

    Article  PubMed  CAS  Google Scholar 

  7. Moni L, Banfi L, Cartagenova D et al (2020) Zinc(II)-mediated diastereoselective Passerini reactions of biocatalytically desymmetrised renewable inputs. Org Chem Front 7:380–398. https://doi.org/10.1039/c9qo00773c

    Article  CAS  Google Scholar 

  8. Li C-J, Anastas PT (2012) Green chemistry: present and future. Chem Soc Rev 41:1413–1414. https://doi.org/10.1039/c1cs90064a

    Article  PubMed  CAS  Google Scholar 

  9. Brun N, Hesemann P, Esposito D (2017) Expanding the biomass derived chemical space. Chem Sci 8:4724–4738. https://doi.org/10.1039/C7SC00936D

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Cao F, Schwartz TJ, McClelland DJ et al (2015) Dehydration of cellulose to levoglucosenone using polar aprotic solvents. Energy Environ Sci 8:1808–1815. https://doi.org/10.1039/C5EE00353A

    Article  CAS  Google Scholar 

  11. Koseki K, Ebata T, Kawakami H et al (1992) US Patent 5,112,994

  12. Court GR, Lawrence CH, Raverty WD, Duncan AJ (2012) US Patent 2012/0111714A1

  13. Kong D, Dolzhenko AV (2022) Cyrene: A bio-based sustainable solvent for organic synthesis. Sust Chem Pharm 25:100591. https://doi.org/10.1016/j.scp.2021.100591

    Article  CAS  Google Scholar 

  14. Camp JE (2018) Bio-available solvent cyrene: synthesis, derivatization, and applications. Chemsuschem 11:3048–3055. https://doi.org/10.1002/cssc.201801420

    Article  PubMed  CAS  Google Scholar 

  15. Stini NA, Gkizis PL, Kokotos CG (2022) Cyrene: a bio-based novel and sustainable solvent for organic synthesis. Green Chem 24:6435–6449. https://doi.org/10.1039/D2GC02332F

    Article  CAS  Google Scholar 

  16. Circa Group (2017) Safety data sheet: CyreneTM. https://www.sigmaaldrich.com/BR/en/sds/SIAL/807796

  17. Sherwood J, de Bruyn M, Constantinou A et al (2014) Dihydrolevoglucosenone (Cyrene) as a bio-based alternative for dipolar aprotic solvents. Chem Commun 50:9650–9652. https://doi.org/10.1039/C4CC04133J

    Article  CAS  Google Scholar 

  18. Prat D, Wells A, Hayler J et al (2016) CHEM21 selection guide of classical- and less classical-solvents. Green Chem 18:288–296. https://doi.org/10.1039/C5GC01008J

    Article  Google Scholar 

  19. Sangon S, Supanchaiyamat N, Sherwood J et al (2020) Direct comparison of safer or sustainable alternative dipolar aprotic solvents for use in carbon–carbon bond formation. React Chem Eng 5:1798–1804. https://doi.org/10.1039/D0RE00174K

    Article  CAS  Google Scholar 

  20. Wilson KL, Kennedy AR, Murray J et al (2016) Scope and limitations of a DMF bio-alternative within Sonogashira cross-coupling and Cacchi-type annulation. Beilstein J Org Chem 12:2005–2011. https://doi.org/10.3762/bjoc.12.187

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Wilson K, Murray J, Jamieson C, Watson A (2018) Cyrene as a bio-based solvent for the Suzuki–Miyaura cross-coupling. Synlett 29:650–654. https://doi.org/10.1055/s-0036-1589143

    Article  CAS  Google Scholar 

  22. Mistry L, Mapesa K, Bousfield TW, Camp JE (2017) Synthesis of ureas in the bio-alternative solvent Cyrene. Green Chem 19:2123–2128. https://doi.org/10.1039/C7GC00908A

    Article  CAS  Google Scholar 

  23. Bousfield TW, Pearce KPR, Nyamini SB et al (2019) Synthesis of amides from acid chlorides and amines in the bio-based solvent Cyrene™. Green Chem 21:3675–3681. https://doi.org/10.1039/C9GC01180C

    Article  CAS  Google Scholar 

  24. Wilson KL, Murray J, Jamieson C, Watson AJB (2018) Cyrene as a bio-based solvent for HATU mediated amide coupling. Org Biomol Chem 16:2851–2854. https://doi.org/10.1039/C8OB00653A

    Article  PubMed  CAS  Google Scholar 

  25. Nickisch R, Conen P, Gabrielsen SM, Meier MAR (2021) A more sustainable isothiocyanate synthesis by amine catalyzed sulfurization of isocyanides with elemental sulfur. RSC Adv 11:3134–3142. https://doi.org/10.1039/D0RA10436A

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  26. Zhang J, White GB, Ryan MD et al (2016) Dihydrolevoglucosenone (Cyrene) as a green alternative to N,N-dimethylformamide (DMF) in MOF synthesis. ACS Sust Chem Eng 4:7186–7192. https://doi.org/10.1021/acssuschemeng.6b02115

    Article  CAS  Google Scholar 

  27. Bonneau G, Peru AAM, Flourat AL, Allais F (2018) Organic solvent- and catalyst-free Baeyer-Villiger oxidation of levoglucosenone and dihydrolevoglucosenone (Cyrene®): a sustainable route to (S)-γ-hydroxymethyl-α,β-butenolide and (S)-γ-hydroxymethyl-γ-butyrolactone. Green Chem 20:2455–2458. https://doi.org/10.1039/C8GC00553B

    Article  CAS  Google Scholar 

  28. Alhifthi A, Harris BL, Goerigk L et al (2017) Structure–reactivity correlations of the abnormal Beckmann reaction of dihydrolevoglucosenone oxime. Org Biomol Chem 15:10105–10115. https://doi.org/10.1039/C7OB02499A

    Article  PubMed  CAS  Google Scholar 

  29. Hughes L, McElroy CR, Whitwood AC, Hunt AJ (2018) Development of pharmaceutically relevant bio-based intermediates though aldol condensation and Claisen–Schmidt reactions of dihydrolevoglucosenone (Cyrene®). Green Chem 20:4423–4427. https://doi.org/10.1039/C8GC01227J

    Article  CAS  Google Scholar 

  30. Hohol RE, Arcure H, Witczak ZJ et al (2018) One-pot synthesis of carbohydrate exo-cyclic enones and hemiketals with 6,8-dioxabicyclo-[3.2.1]octane moieties. Serendipitous formation of a spironolactone when 2-pyridinecarboxaldehyde is used as the reactant Part II. Tetrahedron 74:7303–7309. https://doi.org/10.1016/j.tet.2018.10.049

    Article  CAS  Google Scholar 

  31. Ledingham ET, Stockton KP, Greatrex BW (2017) Efficient synthesis of an indinavir precursor from biomass-derived (−)-levoglucosenone. Aust J Chem 70:1146–1150. https://doi.org/10.1071/CH17227

    Article  CAS  Google Scholar 

  32. Tsypysheva LP, Valeev FA, Spirikhin LV, Tolstikov GA (2000) Stereochemieal differentiation in the reactions of organometallic reagents with levoglucosenone and some of its dihydro derivatives. Russ Chem BuIl Int Ed 49:1237–1240. https://doi.org/10.1007/BF02495766

    Article  CAS  Google Scholar 

  33. Jung ME, Kiankarimi M (1998) Synthesis of methylene-expanded 2′,3″-dideoxyribonucleosides. J Org Chem 63:8133–8144. https://doi.org/10.1021/jo980436l

    Article  CAS  Google Scholar 

  34. Andrade CKZ, Takada SCS, Suarez PAZ, Alves MB (2006) Revisiting the Passerini reaction under eco-friendly reaction conditions. Synlett 2006:1535–1539. https://doi.org/10.1055/s-2006-941606

    Article  CAS  Google Scholar 

  35. Barreto AFS, Vercillo OE, Andrade CKZ (2011) Microwave-assisted Passerini reactions under solvent-free conditions. J Braz Chem Soc 22:462–467. https://doi.org/10.1590/S0103-50532011000300008

    Article  CAS  Google Scholar 

  36. Martinho LA, Rosalba TPF, Andrade CKZ (2022) Passerini reaction to access α-hydroxy amides by facile decarbonylation/decarboxylation of oxalic acid. Eur J Org Chem 2022:e202201199. https://doi.org/10.1002/ejoc.202201199

    Article  CAS  Google Scholar 

  37. Ramozzi R, Morokuma K (2015) Revisiting the Passerini reaction mechanism: existence of the nitrilium, organocatalysis of its formation, and solvent effect. J Org Chem 80:5652–5657. https://doi.org/10.1021/acs.joc.5b00594

    Article  PubMed  CAS  Google Scholar 

  38. Frisch MJ, Trucks GW, Schlegel H et al (2016) Gaussian 16, Rev. C.01. Gaussian Inc., Wallingford, 2016.

  39. Bürgi HB, Dunitz JD, Lehn JM, Wipff G (1974) Stereochemistry of reaction paths at carbonyl centres. Tetrahedron 30:1563–1572. https://doi.org/10.1016/S0040-4020(01)90678-7

    Article  Google Scholar 

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Acknowledgements

The authors thank Universidade de Brasília (Edital DPG 001/2022), FAPDF (Edital 03/2021) and CAPES for financial support, and Sigma-Aldrich Brazil for a sample of Cyrene.

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Authors and Affiliations

  1. Instituto de Química, Laboratório de Química Metodológica e Orgânica Sintética (LaQMOS), Universidade de Brasília, Brasília, DF, Brazil

    Luan A. Martinho, Thaissa P. F. Rosalba & Carlos Kleber Z. Andrade

  2. Instituto de Química, Laboratório de Química Computacional (LQC), Universidade de Brasília, Brasília, DF, Brazil

    Gustavo G. Sousa & José Roberto S. Politi

  3. Instituto de Química, Laboratório de Síntese Inorgânica e Cristalografia (LASIC), Universidade de Brasília, Brasília, DF, Brazil

    Claudia C. Gatto

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  1. Luan A. Martinho
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11030_2023_10618_MOESM1_ESM.docx

Supplementary file1 Typical experimental procedures, NMR and mass spectra of all compounds (PDF), HPLC data for the mixtures of isomers, computational details and crystallographic data for 3a (CIF) (DOCX 150468 KB)

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Martinho, L.A., Rosalba, T.P.F., Sousa, G.G. et al. Cyrene: a very reactive bio-based chiral ketone in diastereoselective Passerini reactions. Mol Divers 28, 111–123 (2024). https://doi.org/10.1007/s11030-023-10618-6

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